Group B streptococci (GBS) are being increasingly recognized as important human pathogens. In addition to causing meningitis, bacteremia, endocarditis, bronchopneumonia, arthritis, peritonitis, wound infections, abscesses, and urinary tract infections in adults, as many as 80% of group B infections occur in neonates (Jelinkova, J. [1977]Current Topics in Microbiology and Immunology 76:127-165). Approximately 30% of pregnant women have been reported to be colonized by GBS. Despite this high carriage rate, neonatal infection occurs with an incidence of only 0.5% (Lim, D. V., Morales, W. J., Walsh, A. F., and Kazanis, D. [1986]J. Clin. Micro. 23:489-492). Predisposing factors to development of disease are premature birth, prolonged rupture of membranes, overt maternal infection, and deficiency of type specific antibody (Boyer, K. M. and Gotoff, S. P. [1986]New England J. Med. 314:1665-1669). To date no one has identified a bacterial marker which would predict which streptococcal strains are more likely to cause infection.
The ability to subtype group B streptococci more comprehensively may be of value in predicting which organisms could cause sepsis, in particular neonatal sepsis. Recently, a receptor for the Fc region of human IgA was reported to be expressed on the surfaces of some strains of GBS (Russell-Jones, G. J., Gotschlich, E. C., and Blake, M. S. [1984] J. Exp. Med. 160:1467-1475). Western blot analysis of proteins extracted from these strains by treatment with detergent indicated that it may in fact be the .beta. antigen component of the c protein marker complex which has the ability to bind to IgA (Russell-Jones, G. J. and Gotschlich, E. C. [1984] J. Exp. Med. 160:1476-1484). Since IgA is the primary line of defense at mucosal surfaces, such as the vaginal epithelium, the ability of bacteria to bind this class of immunoglobulin molecules in a non-immune fashion might interfere with effective clearance of these microorganisms.
GBS are typed based on the presence of type specific carbohydrate antigens expressed on their surfaces, i.e., Ia, Ib, II, III, IV, and V. In addition, a protein marker called the c protein has been used as a typing marker. Subsets of serotype Ia and II and virtually all serotype Ib have been reported to express components of the c protein. The c protein had been reported to consist of two acid extractable antigens called .alpha. and .beta.. A further level of sub-typing of group B streptococci, with respect to the c protein marker complex, would be desirable to identify potential pathogens.
In addition to the need to identify and sub-type GBS, there is also an urgent need to identify means of preventing GBS infections. GBS infections now account for over 40% of all neonatal sepsis in the United States resulting in over 12,000 cases and 2,500 infant deaths annually (Strickland, D. M., E. R. Yeomans, G. D. V. Hankins 1990] Am. J. Obstet. Gynecol. 163:4-8). In addition, pregnancy related morbidity occurs in nearly 50,000 women annually (Baker, C. J. [1989]J. I. D. 161:917-921). The National Academy of Sciences estimated that the cost of GBS early onset sepsis and obstetric disease exceeded $500 million in 1985 and listed GBS as the fourth most important cause of preventable infectious mortality in the United States (Strickland et al., supra). As discussed above, as many as 30% of pregnant women have been reported to be colonized with GBS. Despite this high degree of colonization, only a small percentage of women actually give birth to septic infants. However, those infants who do become infected have a very high rate of morbidity (particularly permanent neurologic damage) and mortality. No GBS vaccine is currently available. Early onset sepsis occurs within hours to days of birth, is associated with vertical transmission from the mother, and is associated with a mortality rate as high as 50-60%. The causative GBS are not clearly delineated within a given serotype. Until recently, no bacterial determinants have been identified which are predictive of early onset sepsis. Late onset GBS sepsis occurs days to weeks after birth, is not necessarily associated with vertical transmission, and is associated primarily with strains expressing the type III carbohydrate. Serotype III GBS are often associated with meningitis. The mortality rate from late onset sepsis is approximately 20%, but neurologic sequelae occur in approximately 50% of patients with meningitis.
Therefore, there is a great need to identify compositions and methods to reduce the susceptibility to GBS infection.